Inappropriate plasma levels of renin contribute to the development and/or maintenance of several forms of hypertension. The sympathetic nervous system is known to play a major role in controlling renin secretion. However, little is known about how the brain is organized to regulate the sympathetic effects on renin release. In the present application, studies are outlined to investigate the interaction between the brain and kidney in relation to the control of renin secretion. Emphasis will be placed on the paraventricular nucleus of the hypothalamus (PVN). Three questions are aimed at determining how direct stimulation of the PVN can influence plasma renin activity (PRA) in conscious rats. 1) Can electrical activation of PVN produce an increase in PRA by a direct action without altering stimuli to other renin regulatory mechanisms? 2) Can electrical activation of PVN enhance the ability of the kidney to respond to a non- neural stimulus for renin secretion? 3) Can a mild stress enhance the sensitivity of the kidney to a non-neural stimulus for renin, and if so, is neural circuitry to or through the PVN involved? Two further questions are aimed at determining the contribution of the PVN to the regulation of renin release by central angiotensin II (AII). 4) In the rat, does central AII increase PRA, and if so, do neural pathways from central AII receptive sites to PVN contribute? 5) Does chemical or electrical activation of the subfornical organ (SFO) increase PRA through a mechanism that involves the PVN? Experiments will be performed in conscious rats instrumented for measurement of arterial pressures, heart rate, and renal blood flow. Electrical stimulation will be delivered to the PVN using stereotaxically implanted electrodes. Blood will be collected before and after the stimulation to determine changes in PRA. In some rats, stimulation of PVN will be performed during suprarenal aortic occlusion, a non-neural stimulus for renin release. A mild stress will be introduced to some rats by directing a jet of air to their faces. The renin response to aortic occlusion will be determined before and during the stress, and in other rats, after chemical ablation of the PVN. The effect of icv AII on PRA will be determined in control and PVN ablated rats. The effect on PRA of activation of the SFO with either electrical current or direct microinjection of AII will also be determined in rats with or without lesions in PVN. These studies have the potential to identify a number of mechanisms whereby the central nervous system can contribute to elevated PRA as found in some forms of hypertension.